Autonomic Regulation of The Cardiovascular system. Cardiac 1. Components of Regulation. 2. Autonomic Component. 3. Receptors. 4. Cardiac, Vascular (Systemic Pulm). 5. Comparative (anatomy). 6. Assessment. 7. Questions. CARDIOVASCULAR FUNCTION: ADULT Transport Function Cardiac output= fh X SV So Factors that alter -fh, or SV Fish fh And SV Terrestrial vertebrates Primary fh CARDIOVASCULAR REGULATION AUTONOMIC (Tone). Sympathetic Parasympathetic FEEDBACK CONTROL Baroreflex LOCAL /Hormonal 1
REFLEXIVE CONTROL Baroreflex Chemoreflex Sympathetic Parasympathetic LOCAL 12 Pharmacological Manipulation Pressure (kpa) 10 8 6 4 Phenyl 20 s LOCAL/HUMORAL MECHANISMS NO Renin Angiotensin Prostaglandins Catecholamines 5HT Endothelin Hydrogen Sulfide Adenosine Histamine NANC Auto regulation AUTONOMIC COMPONENTS Parasympathetic. Neurotransmitter-ACh Cholinergic Receptors. Muscarinic/ nicotinic Sympathetic Adrenergic receptors α and β - ionotropic and Chronotropic 2
AUTONOMIC COMPONENTS Parasympathetic Cholinergic Receptors muscarinic Myogenic Vertebrate Heart Autonomous Depolarization Pacemaker tissue Sino atrial node Sinus Venosus- Exp fish Key- Cardiac tissue is a function syncytia- Pacemaker tissue gn gk gca gk gca gk gca Na permeability- β adrenergic K permeability- Acetylcholine 3
Increase in Contractility Sympathetic β 1 Stimulation G protein Increase Ca ++ Positive Inotropic EKG R-R interval Mammalian CARDIOVASCULAR AUTOTONIC TONE- Parasympathetic Tone Constant Continuous Sympathetic Tone f H f H Increased Contractility-β 4
CARDIOVASCULAR TONE Systemic Vasculature Adrenergic Tone Vessels β receptors α receptors Stimulated by: Release from Sympathetic Release from chromaffin tissue Gills Adrenergic -Vessels CARDIOVASCULAR TONE Gas exchange Vasculature β receptors α receptors Lung Adrenergic - Vessels β receptors Amph,Reptilian Bird. Lung CARDIOVASCULAR TONE Gas exchange Vasculature Cholinergic Pulmonary Vessels Amph Reptiles 5
CARDIOVASCULAR TONE 1. AUTONOMIC Tone Function. a. Allows for precise changes in CO and arterial resistance. b. Meet metabolic demands 2. Vagus and Sympathetic nerves Phylogeny of Cardiac Inneration Taylor and Wang 2009 Peripheral Vessels Adrenergic Innervation? Both α and β Both α and β 6
CARDIOVASCULAR TONE Anatomic Comparison Elasmobranch Parasympathetic- present Sympathetic - absent Anatomic Comparison Teleost Fish Vago-sympathetic trunk Parasympathetic - present Sympathetic present lost in some species Possible Question What conditions allowed Loss Anatomic Comparison Amphibians Vago-sympathetic trunk Parasympathetic - present Sympathetic - present 7
Anatomic Comparisons Cont. Reptilian Parasympathetic - present Sympathetic - present Anatomic Comparisons Cont. Mammalian (Avian) Parasympathetic - present Sympathetic - present Important Point: Anatomical Data Needs to Coupled to Pharmacological Data METHODS OF ASSESSMENT Direct Cardiovascular Measurements Ablation -Denervation -limited to cardiac innervation -Difficult in Fish and Amph. Pharmacology -Drug Treatment- Involving Blockade, Depletion, restricted release. -selective blockade can up-regulation other systems. 8
PHARMACOLOGY AS A TOOL OF INVESTIGATION X X Drug X Peripheral Central -Receptor Blockade -Ganglionic Blockade -Sympathectomy -Terminal depletion. PHARMACOLOGY AS A TOOL OF INVESTIGATION -Receptor Blockade- competitive antagonist A. Cholinergic - Atropine B. β-adrenergic- Proporanolol 1-2- practolol C. α-adrenergic- phenotamine 1- prazosin 2- yohimbine -Ganglionic Blockade - Hexamethonium- nicotinic block -Sympathectomy- 6-Hydroxydopamine storage impaired -Terminal depletion- Reserpine - inhibit release - Brytilium EXAMPLE β-tone ASSESMENT Receptor blockade ΔP mean (kpa) 0.6 0.4 0.2 0-0.2-0.4-0.6 * * * Δf H (min -1 ) 0-10 -20-30 -40-50 -60 * * * * * 9
SYMPATHECTOMY P mean (kpa) f H (min -1 ) P mean (kpa) 5 4 3 2 1 f H (min -1 ) 350 300 250 200 150 Incubation Period (%) WHAT IS THE SOURCE? ΔP mean (kpa) 0.6 0.4 0.2 0-0.2-0.4-0.6 * * * Δf H (min -1 ) 0-10 -20-30 -40-50 -60 * * * * * Incubation Period (%) Crossley et al 2003 AUTONOMIC TONE Comparison Elasmobranch - have adrenergic tone (cardiac and vascular);vagal tone cardiac No sympathetic innervation Teleosts- have adrenergic tone (cardiac, vascular) vagal tone (cardiac). Amphibians- have adrenergic tone (cardiac, vascular) vagal tone (cardiac and pulmocutaneous vessel). Reptiles- have adrenergic tone (cardiac, vascular) vagal tone (cardiac and pulmonary artery vessel). Mammals and Birds - have adrenergic tone (cardiac, vascular) vagal tone (cardiac). 10
Interprate this Finding TONE CALCULATION 1. Questions How does Each tonus Compare? How does Activity effect tonus? How does Species compare? f H antagonist - f H control f H intrinsic How do Animals Compare at different Life Stages Ect. PHARMOCOLOGY: Drugs and Sympathectomy/Ganglionic - 6-Hydroxydopamine - Hexamethonium 11